title: Antisense oligonucleotide suppression of human IGF-1R inhibits the growth and survival of in vitro cultured epithelial ovarian cancer cells.
abstract: BACKGROUND
  Preclinical evaluation of the anti-neoplastic activity of antisense oligonucleotide (AS) suppression of human insulin-like growth factor I receptor (IGF-IR) in human epithelial ovarian cancer (EOC).
  
  
  METHODS
  Ovarian cancer cells from 36 patients with EOC were investigated under serum-free tissue culture conditions. IGF-I production was evaluated by standard ELISA. IGF-IR and phosphorylated IRS-1, AKT, and MAP kinase expression and protein levels were evaluated by immunohistochemistry and Western blotting. Cancer cell growth and proliferation assays were performed in triplicates using MTT assay. Apoptosis was evaluated by TUNNEL assay.
  
  
  RESULTS
  All ovarian cancer tissue samples tested produced IGF-I and expressed IGF-IR, supporting the existence of an autocrine loop. Treatment of primary ovarian cancer cell lines with an IGF-1R AS inhibited growth and proliferation and decreased clonogenicity in soft agar assay. AS treatment was demonstrated to inhibit the expression of IGF-1R and decrease the concentration of phosphorylated IRS-1, AKT, and MAP kinase signaling protein downstream of the IGF-IR. We also observed that the IGF-1R AS sensitized cancer cell lines to cisplatin in vitro through the PI3K pathway.
  
  
  CONCLUSIONS
  IGF-IR enhances the proliferation and tumorigenicity of human ovarian cancer cells and inhibition of IGF-IR by AS oligonucleotide treatment potentiates the activity of cisplatin in vitro. Therefore, IGF-1R is a potential molecular target in ovarian cancer.
authors.affiliation: Department of Gynecologic Oncology, Hunan Provincial Tumor Hospital, Xianjiahu Rd, Changsha, Hunan 410006, China. tanjie_hospital@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Junjun
authors.initials: J
authors.lastname: Li
authors.forename: Guqing
authors.initials: G
authors.lastname: Zeng
authors.forename: Yanxiang
authors.initials: Y
authors.lastname: Tang
authors.forename: Wenfang
authors.initials: W
authors.lastname: Tian
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: J Philippe
authors.initials: JP
authors.lastname: York
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xia